| PartⅠPolymorphisms in XPG Gene in Nucleotide-excision Repair Pathway and Susceptibility to Lung CancerLung cancer is the major cause of cancer-related death in the world,and smoking is known as the predominant environmental risk factor for it.Tobacco-related carcinogenic compounds and their metabolites cause a variety of DNA damage that may result in genetic instability,mutagenesis,and then lead to cell death or carcinogenesis.There are mainly four DNA repair pathways in cell to maintain the genomic integrity and prevent these detrimental consequences.Among them, nucleotide-excision repair(NER) plays a critical role in repairing DNA damage induced by smoking.The xeroderma pigrnentosum complementary group G(XPG,ERCC5) is an essential gene in NER pathway.To assess the association between XPG SNPs and lung cancer risk,11 representative SNPs in XPG were genotyped by the Illumina genotyping platform among 500 incident lung cancer patients and 517 age-and gender-matched controls,and then a case-control study was performed based on the genotype data.No association was found between these 11 SNPs and lung cancer risk during the single locus analysis.During the stratified analysis,we found 4 of the 11 SNPs in XPG could interact with age and smoking status(in the group which age≤60: rs1998876 P=0.003;rs4150348 P=0.005;rs4150360 P=0.003;rs17655 P=0.02; in the non-smoker group:rs1998876 P=0.02;rs4150348 P=0.03;rs4150360 P= 0.03;rs17655 P=0.04;assessed with recessive model,respectively),suggesting that these SNPs may influence lung cancer susceptibility by the interaction with environmental factors.Haplotypes of XPG were found no association with lung cancer susceptibility. In conclusion,we analyzed the association between SNPs in XPG gene and lung cancer risk,and we revealed that several SNPs in XPG gene may contribute to the lung cancer risk by interacting with environmental factors.It can be used as a criteria of the filtration of high lung cancer risk cohort. PartⅡAssociation between XPG C3507G Polymorphism and Cancer Risk:A Meta-analysisPolymorphisms in the DNA repair genes that are involved in the nucleotide-excision repair(NER) pathway may affect the cancer susceptibility.The xeroderma pigmentosum complementary group G(XPG,ERCC5),one of the NER genes,has an extensively studied polymorphism C3507G(rs17655).As these published studies are not conclusive,we performed a meta-analysis from all eligible case-control studies about this polymorphism.Overall,the 3507C allele(10603 cancer patients and 12261 controls) showed no significant effect on cancer risk compared to 3507G allele(P=0.718,OR=1.01, 95%CI(0.95-1.08)).Meta-analysis under other genetic also did not reveal any association between C3507G and cancer risk.We also performed a subgroup analysis to clarify the association of cancer risk with it in different ethnicities(Caucasian and non Caucasian),and there were no significant variance of cancer risk shown when we compared 3507C allele to 3507G allele in both of the subgroups(P=0.476,OR=1.08,95%CI(0.87-1.34) for Caucasian descent,and P=0.848,OR=1.01,95%CI(0.96-1.06) for non Caucasian decent).No evidence of any association was found when we performed subgroup analysis under all the other genetic models,as well.More studies based on larger,stratified case-control population are needed to further evaluate the role of XPG 3507G polymorphism in cancer risk. |
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